INTRINSIC LETHALITY OF CHLORIDE-CHANNEL-DIRECTED INSECTICIDES AND CONVULSANTS IN MAMMALS
INTRINSIC LETHALITY OF CHLORIDE-CHANNEL-DIRECTED INSECTICIDES AND CONVULSANTS IN MAMMALS
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DOI：
10.1016/0378-4274(92)90287-t
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发表时间：
1992-05-01
影响因子：
3.5
通讯作者：
BLOOMQUIST, JR
中科院分区：
文献类型：
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作者：
BLOOMQUIST, JR
通过向小鼠脑内注射来测定一系列氯离子通道定向惊厥剂和杀虫剂的内在致死率。与报道的腹膜内 LD50 相比，环二烯类杀虫剂和印防己毒素的毒性通过脑内注射而增强。相比之下，林丹、阿维菌素、双环惊厥药 TBPS 和 TBOB 类似物的毒性在两种给药途径下大致相同。这些结果表明，大脑是环二烯类和印防己毒素的主要靶位，而周围神经系统在林丹、阿维菌素和双环惊厥药（如 TBPS）的毒性作用中可能相对更重要。除印防己毒素外，这些化合物总体上显示出急性脑内毒性与抑制 GABA 依赖性氯离子吸收的效力之间存在良好的相关性。讨论了多种氯离子通道亚型作为这些化合物的靶标的证据，以及这对这些研究结果的潜在影响。
The intrinsic lethality of a series of chloride-channel-directed convulsants and insecticides was determined by intracerebral injection into mice. The toxicities of the cyclodiene insecticides and picrotoxinin were potentiated by intracerebral injection, when compared to their reported intraperitoneal LD50s. In contrast, the toxicities of lindane, abamectin, and the bicyclic convulsants TBPS and a TBOB analog were approximately the same by either route of administration. These results suggest that the brain is the primary target site for the cyclodienes and picrotoxinin, while the peripheral nervous system may be relatively more important in the toxic action of lindane, abamectin, and bicyclic convulsants such as TBPS. With the exception of picrotoxinin, these compounds showed, overall, a good correlation between acute intracerebral toxicity and potency for inhibiting GABA-dependent chloride uptake. The evidence that multiple chloride-channel subtypes serve as targets for these compounds and the potential impact this had on the results of these studies are discussed.